Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality
Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here, we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recr...
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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:2e94cb6d6a9c41b5846a76df7755308e2021-12-03T15:37:23ZNeutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality10.7554/eLife.694172050-084Xe69417https://doaj.org/article/2e94cb6d6a9c41b5846a76df7755308e2021-11-01T00:00:00Zhttps://elifesciences.org/articles/69417https://doaj.org/toc/2050-084XHuman serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here, we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 39 patients who were followed up for a median of 12.5 days (1–35 days), among them 23 had died. Analyzing blood samples from patients and healthy individuals (n=11), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance spectra of spin-labeled fatty acids (SLFAs) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10–11). Non-survivors’ HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and smaller S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Following loading/unloading of 16-DSA, we show that the transport function of HSA may be impaired in severe patients. Stratified at the means, Kaplan–Meier survival analysis indicated that lower values of S/W ratio and accumulated H2O2 in plasma significantly predicted in-hospital mortality (S/W≤0.15, 81.8% (18/22) vs. S/W>0.15, 18.2% (4/22), p=0.023; plasma [H2O2]>8.6 μM, 65.2% (15/23) vs. 34.8% (8/23), p=0.043). When we combined these two parameters as the ratio ((S/W)/[H2O2]) to derive a risk score, the resultant risk score lower than the mean (<0.019) predicted mortality with high fidelity (95.5% (21/22) vs. 4.5% (1/22), log-rank χ2=12.1, p=4.9×10−4). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements and/or oxidative stress.Mohamed A BadawyBasma A YasseenRiem M El-MessieryEngy A Abdel-RahmanAya A ElkhodiryAzza G KamelHajar El-sayedAsmaa M ShedraRehab HamdyMona ZidanDiaa Al-RaawiMahmoud HammadNahla ElsharkawyMohamed El AnsaryAhmed Al-HalfawyAlaa ElhadadAshraf HatemSherif AbouelnagaLaura L DuganSameh Saad AlieLife Sciences Publications Ltdarticlecritically ill COVID-19 patientsCOVID-19 mortalityneutrophilsoxidative stresshuman serum albumin damageMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
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EN |
| topic |
critically ill COVID-19 patients COVID-19 mortality neutrophils oxidative stress human serum albumin damage Medicine R Science Q Biology (General) QH301-705.5 |
| spellingShingle |
critically ill COVID-19 patients COVID-19 mortality neutrophils oxidative stress human serum albumin damage Medicine R Science Q Biology (General) QH301-705.5 Mohamed A Badawy Basma A Yasseen Riem M El-Messiery Engy A Abdel-Rahman Aya A Elkhodiry Azza G Kamel Hajar El-sayed Asmaa M Shedra Rehab Hamdy Mona Zidan Diaa Al-Raawi Mahmoud Hammad Nahla Elsharkawy Mohamed El Ansary Ahmed Al-Halfawy Alaa Elhadad Ashraf Hatem Sherif Abouelnaga Laura L Dugan Sameh Saad Ali Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality |
| description |
Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here, we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 39 patients who were followed up for a median of 12.5 days (1–35 days), among them 23 had died. Analyzing blood samples from patients and healthy individuals (n=11), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance spectra of spin-labeled fatty acids (SLFAs) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10–11). Non-survivors’ HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and smaller S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Following loading/unloading of 16-DSA, we show that the transport function of HSA may be impaired in severe patients. Stratified at the means, Kaplan–Meier survival analysis indicated that lower values of S/W ratio and accumulated H2O2 in plasma significantly predicted in-hospital mortality (S/W≤0.15, 81.8% (18/22) vs. S/W>0.15, 18.2% (4/22), p=0.023; plasma [H2O2]>8.6 μM, 65.2% (15/23) vs. 34.8% (8/23), p=0.043). When we combined these two parameters as the ratio ((S/W)/[H2O2]) to derive a risk score, the resultant risk score lower than the mean (<0.019) predicted mortality with high fidelity (95.5% (21/22) vs. 4.5% (1/22), log-rank χ2=12.1, p=4.9×10−4). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements and/or oxidative stress. |
| format |
article |
| author |
Mohamed A Badawy Basma A Yasseen Riem M El-Messiery Engy A Abdel-Rahman Aya A Elkhodiry Azza G Kamel Hajar El-sayed Asmaa M Shedra Rehab Hamdy Mona Zidan Diaa Al-Raawi Mahmoud Hammad Nahla Elsharkawy Mohamed El Ansary Ahmed Al-Halfawy Alaa Elhadad Ashraf Hatem Sherif Abouelnaga Laura L Dugan Sameh Saad Ali |
| author_facet |
Mohamed A Badawy Basma A Yasseen Riem M El-Messiery Engy A Abdel-Rahman Aya A Elkhodiry Azza G Kamel Hajar El-sayed Asmaa M Shedra Rehab Hamdy Mona Zidan Diaa Al-Raawi Mahmoud Hammad Nahla Elsharkawy Mohamed El Ansary Ahmed Al-Halfawy Alaa Elhadad Ashraf Hatem Sherif Abouelnaga Laura L Dugan Sameh Saad Ali |
| author_sort |
Mohamed A Badawy |
| title |
Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality |
| title_short |
Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality |
| title_full |
Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality |
| title_fullStr |
Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality |
| title_full_unstemmed |
Neutrophil-mediated oxidative stress and albumin structural damage predict COVID-19-associated mortality |
| title_sort |
neutrophil-mediated oxidative stress and albumin structural damage predict covid-19-associated mortality |
| publisher |
eLife Sciences Publications Ltd |
| publishDate |
2021 |
| url |
https://doaj.org/article/2e94cb6d6a9c41b5846a76df7755308e |
| work_keys_str_mv |
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| _version_ |
1718373136451239936 |